LODINE (Page 5 of 6)

ADVERSE REACTIONS

In patients taking etodolac capsules and tablets or other NSAIDs, the most frequently reported adverse experiences occurring in approximately 1-10% of patients are:

Gastrointestinal experiences including: abdominal pain, constipation, diarrhea, dyspepsia, flatulence, gross bleeding/perforation, heartburn, nausea, GI ulcers (gastric/duodenal), vomiting.

Other events including: abnormal renal function, anemia, dizziness, edema, elevated liver enzymes, headaches, increased bleeding time, pruritis, rashes, tinnitus.

Adverse-reaction information for etodolac was derived from 2,629 arthritic patients treated with etodolac capsules and tablets in double-blind and open-label clinical trials of 4 to 320 weeks in duration and worldwide postmarketing surveillance studies. In clinical trials, most adverse reactions were mild and transient. The discontinuation rate in controlled clinical trials, because of adverse events, was up to 10% for patients treated with etodolac.

New patient complaints (with an incidence greater than or equal to 1%) are listed below by body system. The incidences were determined from clinical trials involving 465 patients with osteoarthritis treated with 300 to 500 mg of etodolac b.i.d. (i.e., 600 to 1000 mg/day).

Incidence Greater Than Or Equal To 1% — Probably Causally Related

Body as a whole — Chills and fever.

Digestive system — Dyspepsia (10%), abdominal pain¹ , diarrhea¹ , flatulence¹ , nausea¹ , abdominal distension, epigastric pain, abnormal stools, constipation, gastritis, melena, vomiting.

Nervous system — Asthenia/malaise¹ , dizziness¹ , depression, nervousness, fatigue.

Skin and appendages — Pruritus, rash.

Special senses — Blurred vision, tinnitus.

Urogenital system — Dysuria, urinary frequency.

Musculoskeletal—Arthralgia.

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¹ Drug-related patient complaints occurring in 3 to 9% of patients treated with etodolac. Drug-related patient complaints occurring in fewer than 3%, but more than 1%, are unmarked.

Incidence Less Than 1% — Probably Causally Related

(Adverse reactions reported only in worldwide postmarketing experience, not seen in clinical trials, are considered rarer and are italicized.)

Body as a whole — Allergic reaction, anaphylactic/ anaphylactoid reactions (including shock).

Cardiovascular system — Hypertension, congestive heart failure, flushing, palpitations, syncope, vasculitis (including necrotizing and allergic).

Digestive system — Thirst, dry mouth, ulcerative stomatitis, anorexia, eructation, elevated liver enzymes, cholestatic hepatitis, hepatitis,cholestatic jaundice, duodenitis , jaundice, hepatic failure, liver necrosis, peptic ulcer with or without bleeding and/or perforation, intestinal ulceration, pancreatitis.

Hemic and lymphatic system — Ecchymosis, anemia, thrombocytopenia, bleeding time increased, agranulocytosis , hemolytic anemia, aplastic anemia, leukopenia , neutropenia , pancytopenia .

Metabolic and nutritional — Edema, serum creatinine increase, hyperglycemia in previously controlled diabetic patients.

Nervous system — Insomnia, somnolence.

Respiratory system — Asthma, pulmonary infiltration with eosinophilia.

Skin and appendages — Angioedema, sweating, urticaria, exfoliative dermatitis, vesiculobullous rash, cutaneous vasculitis with purpura , Stevens-Johnson Syndrome, toxic epidermal necrolysis , leukocytoclastic vasculitis , hyperpigmentation, erythema multiforme .

Special senses — Photophobia, transient visual disturbances.

Urogenital system — Elevated BUN, renal failure, renal insufficiency, renal papillary necrosis.

Incidence Less Than 1% — Causal Relationship Unknown

(Medical events occurring under circumstances where causal relationship to etodolac is uncertain. These reactions are listed as alerting information for physicians.)

Body as a whole — Infection, headache.

Cardiovascular system — Arrhythmias, myocardial infarction, cerebrovascular accident.

Digestive system — Esophagitis with or without stricture or cardiospasm, colitis, GI discomfort, burning sensation, blood in stools, gastralgia, upper abdominal discomfort.

Metabolic and nutritional — Change in weight.

Nervous system — Paresthesia, confusion, irritability.

Respiratory system — Bronchitis, bronchospasm, dyspnea, pharyngitis, rhinitis, sinusitis.

Skin and appendages — Alopecia, maculopapular rash, photosensitivity, skin peeling.

Special senses — Conjunctivitis, deafness, taste perversion, loss of taste.

Urogenital system — Cystitis, hematuria, leukorrhea, renal calculus, interstitial nephritis, uterine bleeding irregularities, renal impairment.

Musculoskeletal—Muscle pain.

Additional Adverse Reactions Reported with NSAIDs

Body as a whole — Sepsis, death

Cardiovascular system – Tachycardia

Digestive system — Gastric ulcers, gastritis, gastrointestinal bleeding, glossitis, hematemesis

Hemic and lymphatic system – Lymphadenopathy

Nervous system — Anxiety, dream abnormalities, convulsions, coma, hallucinations, meningitis, tremors, vertigo

Respiratory system — Respiratory depression, pneumonia

Urogenital system — Oliguria/polyuria, proteinuria

OVERDOSAGE

Symptoms following acute NSAID overdose are usually limited to lethargy, drowsiness, nausea, vomiting, and epigastric pain, which are generally reversible with supportive care. Gastrointestinal bleeding can occur and coma has occurred following massive ibuprofen or mefenamic-acid overdose. Hypertension, acute renal failure, and respiratory depression may occur but are rare. Anaphylactoid reactions have been reported with therapeutic ingestion of NSAIDs, and may occur following overdose. Patients should be managed by symptomatic and supportive care following an NSAID overdose.

There are no specific antidotes. Emesis and/or activated charcoal (60 to 100 g in adults, 1 to 2 g/kg in children) and/or osmotic cathartic may be indicated in patients seen within 4 hours of ingestion with symptoms or following a large overdose (5 to 10 times the usual dose). Forced diuresis, alkalinization of the urine, hemodialysis, or hemoperfusion would probably not be useful due to etodolac’s high protein binding.

DOSAGE AND ADMINISTRATION

Carefully consider the potential benefits and risks of etodolac capsules and tablets and other treatment options before deciding to use etodolac capsules and tablets. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS).

After observing the response to initial therapy with etodolac capsules and tablets, the dose and frequency should be adjusted to suit an individual patient’s needs.

Dosage adjustment of etodolac capsules and tablets is generally not required in patients with mild to moderate renal impairment. Etodolac should be used with caution in such patients, because, as with other NSAIDs, it may further decrease renal function in some patients with impaired renal function (see WARNINGS, Renal Effects).

Analgesia

The recommended total daily dose of etodolac for acute pain is up to 1000 mg, given as 200-400 mg every 6 to 8 hours. Doses of etodolac greater than 1000 mg/day have not been adequately evaluated in well-controlled trials.

Osteoarthritis and Rheumatoid Arthritis

The recommended starting dose of etodolac for the management of the signs and symptoms of osteoarthritis or rheumatoid arthritis is: 300 mg b.i.d., t.i.d., or 400 mg b.i.d., or 500 mg b.i.d. A lower dose of 600 mg/day may suffice for long-term administration. Physicians should be aware that doses above 1000 mg/day have not been adequately evaluated in well-controlled clinical trials.

In chronic conditions, a therapeutic response to therapy with etodolac is sometimes seen within one week of therapy, but most often is observed by two weeks. After a satisfactory response has been achieved, the patient’s dose should be reviewed and adjusted as required.

HOW SUPPLIED

Lodine Tablets, USP

400 mg tablets (peach, oval shaped, film coated tablet engraved with “T88” on one side and other side plain)

-in bottles of 30, NDC 69036-503-30

Store at 20°-25°C (68°-77°F) [see USP Controlled Room Temperature]. Store tablets in original container until ready to use. Dispense in light-resistant container.

Medication Guide for Nonsteroidal Anti-inflammatory Drugs (NSAIDs)

What is the most important information I should know about medicines called Nonsteroidal Anti-inflammatory Drugs (NSAIDs)?

NSAIDs can cause serious side effects, including:

• Increased risk of a heart attack or stroke that can lead to death. This risk may happen early in treatment and may increase:
  ○ with increasing doses of NSAIDs
  ○ with longer use of NSAIDs

Do not take NSAIDs right before or after a heart surgery called a “coronary artery bypass graft (CABG).”

Avoid taking NSAIDs after a recent heart attack, unless your healthcare provider tells you to.

You may have an increased risk of another heart attack if you take NSAIDs after a recent heart attack.

• Increased risk of bleeding, ulcers, and tears (perforation) of the esophagus (tube leading from the mouth to the stomach), stomach and intestines:
  ○ anytime during use
  ○ without warning symptoms
  ○ that may cause death

The risk of getting an ulcer or bleeding increases with:

• past history of stomach ulcers, or stomach or intestinal bleeding with use of NSAIDs
  
• taking medicines called “corticosteroids”, “anticoagulants”, “SSRIs”, or “SNRIs”
  
• increasing doses of NSAIDs
  
• longer use of NSAIDs
  
• smoking
  
• drinking alcohol
  
• older age
  
• poor health
  
• advanced liver disease
  
• bleeding problems

NSAIDs should only be used:

• exactly as prescribed
  
• at the lowest dose possible for your treatment
  
• for the shortest time needed

What are NSAIDs?

NSAIDs are used to treat pain and redness, swelling, and heat (inflammation) from medical conditions such as different types of arthritis, menstrual cramps, and other types of short-term pain.

Who should not take NSAIDs?

Do not take NSAIDs:

• if you have had an asthma attack, hives, or other allergic reaction with aspirin or any other NSAIDs.
  
• right before or after heart bypass surgery.

Before taking NSAIDs, tell your healthcare provider about all of your medical conditions, including if you:

• have liver or kidney problems
  
• have high blood pressure
  
• have asthma
  
• are pregnant or plan to become pregnant. Talk to your healthcare provider if you are considering taking NSAIDs during pregnancy. You should not take NSAIDs after 29 weeks of pregnancy .
  
• are breastfeeding or plan to breast feed

Tell your healthcare provider about all of the medicines you take, including prescription or over-the-counter medicines, vitamins or herbal supplements . NSAIDs and some other medicines can interact with each other and cause serious side effects. Do not start taking any new medicine without talking to your healthcare provider first.

What are the possible side effects of NSAIDs?

NSAIDs can cause serious side effects, including:

See “What is the most important information I should know about medicines called Nonsteroidal Anti-inflammatory Drugs (NSAIDs)?

• new or worse high blood pressure
  
• heart failure
  
• liver problems including liver failure
  
• kidney problems including kidney failure
  
• low red blood cells (anemia)
  
• life-threatening skin reactions
  
• life-threatening allergic reactions
  
• Other side effects of NSAIDs include: stomach pain, constipation, diarrhea, gas, heartburn, nausea, vomiting, and dizziness

Get emergency help right away if you get any of the following symptoms:

• shortness of breath or trouble breathing
  
• slurred speech
  
• chest pain
  
• swelling of the face or throat
  
• weakness in one part or side of your body

Stop taking your NSAID and call your healthcare provider right away if you get any of the following symptoms:

• nausea
  
• vomit blood
  
• more tired or weaker than usual
  
• there is blood in your bowel movement or it is black and sticky like tar
  
• diarrhea
  
• unusual weight gain
  
• itching
  
• your skin or eyes look yellow
  
• skin rash or blisters with fever
  
• indigestion or stomach pain
  
• swelling of the arms, legs, hands and feet
  
• flu-like symptoms

If you take too much of your NSAID, call your healthcare provider or get medical help right away.

These are not all the possible side effects of NSAIDs. For more information, ask your healthcare provider or pharmacist about NSAIDs.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Other information about NSAIDs

• Aspirin is an NSAID but it does not increase the chance of a heart attack. Aspirin can cause bleeding in the brain, stomach, and intestines. Aspirin can also cause ulcers in the stomach and intestines.
  
• Some NSAIDs are sold in lower doses without a prescription (over-the-counter). Talk to your healthcare provider before using over-the-counter NSAIDs for more than 10 days.

General information about the safe and effective use of NSAIDs

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide.

Do not use NSAIDs for a condition for which it was not prescribed. Do not give NSAIDs to other people, even if they have the same symptoms that you have. It may harm them.

If you would like more information about NSAIDs, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about NSAIDs that is written for health professionals.

Mfd. by: Taro Pharmaceutical Industries Ltd.,

Haifa Bay, Israel 26110

Packaged for and Distributed by: Sallus Laboratories, LLC

Birmingham, AL 35242

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Revised: September 2016